The MIT Program of 'Molecular Analysis of Cardiovascular Biology and Pathology'will investigate the molecular biology of the heart and vasculature, and the abnormalities that lead to cardiovascular disorders. Its main goals are to identify biochemical, cell biologic, and genetic determinants that underlie normal cardiac and vascular development and function, and that, when altered, predispose to or cause cardiovascular diseases. The work will focus on murine models of physiology and pathology and it will employ state-of-the-art strategies of molecular and cellular biology and genetics. This work is expected to contribute significantly to the elucidation of the basic molecular physiologic mechanisms required for future targeted advances in the diagnosis, treatment and prevention of cardiovascular disease. The Program will foster extensive ongoing interactions among three faculty members in MIT's Department of Biology and one from the CBR Institute and Harvard Medical School. These investigators employ a variety of molecular biologic, genetic and physiologic approaches to study the structure and function of the cardiovascular system. They have been establishing the structure, function, and regulation of certain critical genes and their protein products;uncovering key pathways with somatic cell and molecular genetic techniques, and elucidating the biologic effects of specific genes at the whole organism level by employing transgenic/chimeric/knockout mouse models. The nature of the various projects involves extensive collaboration among Program participants, who will contribute a wide variety of molecular, cellular, genetic, genomics and physiologic approaches to the resolution of common problems. The overall Program will be strengthened by shared facilities for Murine Genetics and Physiology, Cell Biology and Administration. We expect that the proposed network of interactions, which build on a successful 16+ year history of this program, will accelerate research accomplishments in the individual laboratories and significantly contribute to our understanding of cardiovascular physiology and pathophysiology.